Amyloid plaques, which cause neurodegeneration in the brains of Alzheimer's disease (AD) patients, are composed of amyloid-β (A β) peptides produced from cleavages of amyloid precursor protein (APP) by β- and γ-secretase. Therapeutic approaches to treating AD in the past decade have centered on the prevention of Aβ production, such as augmentation of β-secretase activity to reduce production of A β, or inhibition of β-γ-secretase activities. Unfortunately, the non-selective inhibition of β- and γ-secretases results in unavoidable side elects due to interference with other physiological substrates of β- and γ-secretases.
ErbB2 is tightly associated with neuritic plaques in AD. Autophagy controls the clearance of misfolded proteins and damaged organelles, and plays an essential role in maintaining neuronal functions. Whether farther ErbB2 inhibition could increase autophagic flux remains elusive.